1. Technical Field
This disclosure relates to methods for assessing myocardial angiogenesis using contrast agents and imaging techniques, such as, for example, magnetic resonance imaging (MRI).
2. Background of Related Art
Angiogenesis (also known as neovascularization) in mature adult tissues is a tightly regulated process that can occur in a number physiological and pathophysiological conditions. In particular, myocardial collateral vessels in coronary circulation can develop in response to progressive coronary artery occlusion. These coronary collaterals are natural bypass vessels that can develop in the ischemic areas of the heart to provide an alternate route for nutrient blood supply. Typical myocardial collaterals are small thin-walled vessels, ranging from about forty to about two hundred micrometers in diameter, and their presence is an indication of advanced coronary disease. Although coronary collaterals are not detected in all patients with advanced coronary disease, their presence is associated with smaller infarcts and a more benign clinical course. Sufficient collateralization can prevent the damage of heart attack. For this reason, identification of collateral circulation is clinically important. Despite its value, identification of collateralized tissue has to date been quite limited due to the insensitivity of presently available detection techniques.
Clinical agents that are currently in use detect blood capillaries. However, these agents leak out of the vasculature rapidly and have no special signal associated with newly sprouting capillaries induced by angiogenesis. Thus, the monitoring of capillary number and condition is both complex and prone to error using the presently available agents.
The difference between new and normal capillaries is further masked by the fact that the presently used clinical agent freely crosses most normal endothelium as well as new angiogenic endothelium. The monitoring of therapy to revive damaged myocardium must be sensitive to the induction of new blood vessels so that the efficacy of the therapy can be closely monitored and if necessary the therapy can be altered quickly to be more efficacious.
Therefore, it would be advantageous to be able to generate a more specific signal related to the growth of new endothelium to correctly monitor the course of therapy and reduce delay in the adjustment of the course of treatment.